A study of the P2X7 purinoceptor and vascular ATP metabolic pathways in chronic kidney disease-associated arterial calcification

The risk of cardiovascular-related death is several-fold higher in patients with chronic kidney disease (CKD) compared with the general population. Arterial calcification (AC) is extremely common in patients with CKD and strongly associates with cardiovascular-related mortality, however, there are currently no specific treatments to prevent its development and/or progression. Abundant evidence now suggests that AC is cell-mediated and actively-regulated, involving mechanisms linked to bone homeostasis, production of calcification inhibitors and vascular smooth muscle cell (VSMC) function. The P2X7 receptor (P2X7R) is an ATP-sensitive cation channel which has been implicated in several biological processes, in non-vascular contexts, thought to be important in the aetiology of AC. In addition, disruption to the normal function of some enzymes involved in ATP metabolism has been shown to contribute to AC, although little is known about their role in CKD-related arterial calcium deposition. The work in this thesis tested the primary hypothesis that P2X7R contributes to the pathogenesis of CKD-associated AC. Preliminary work was also conducted to examine the expression of components of the ATP-metabolising system in this clinical setting. P2X7R expression was confirmed in human and rodent vascular smooth muscle but was un-affected by calcification. In vitro, the P2X7R-specific antagonist, A438079, did not influence calcium deposition occurring in the presence of human VSMCs or segments of rat aorta exposed to ‘calcification-promoting’ medium. Calcification of cultured rat aorta was also not influenced by a second P2X7R-specific antagonist, A839977, or by BzATP (a receptor agonist). Aortic rings from mice deficient in P2X7R calcified to a similar extent to wild-type controls in vitro. A novel, adenine-based mouse model was developed to evaluate the effect of P2X7R gene deficiency on CKD-associated AC in vivo. However, the number of mice exhibiting AC in the final experiment was too low to draw any firm conclusion. Therefore, rats were fed an adenine-containing, high phosphate diet for 4 weeks (to induce CKD and AC) and administered a selective P2X7R antagonist, twice daily, throughout this period. Pharmacological blockade of P2X7R did not influence the magnitude of aortic calcification in this model. Quantification of mRNA performed on tissue obtained from the in vivo rat experiment suggested that VSMC-specific markers are down-regulated in calcified arteries, although VSMC osteogenic transformation, which is widely reported in the literature to occur in the context of AC, was not detected. Expression of the apoptosis marker, caspase-3, was increased in calcified arteries in vivo. P2X7R blockade did not influence any of these changes in mRNA expression. Expression of mRNA for ENPP-1, an ATP-metabolising enzyme responsible for the generation of the calcification inhibitor, pyrophosphate (PPi), was significantly increased in calcified arteries from CKD rats. Functional activity of ENPP-1 was also increased in these vessels. The expression of mRNA for other components of the ATP-metabolising system was also in keeping with an attempt by VSMCs to generate more PPi, possibly as an adaptive, defensive response to uraemic, calcification-promoting factors. Furthermore, an increase in ENPP-1 mRNA expression was detected in calcified inferior epigastric arteries from patients with end-stage renal disease (extracted at the time of kidney transplantation). In summary, P2X7R does not appear to contribute to the pathogenesis of CKD-associated AC, although this should be confirmed in experimental models which more closely simulate human disease. Arterial expression of enzymes involved in the metabolism of ATP does seem to change in AC. Future work should therefore focus on gauging the clinical relevance of this in order to better understand the mechanisms underlying the disease and potentially develop new therapeutic interventions

Quality of perception to quality of service mapping using a dynamically reconfigurable communication system

We present an innovative approach for providing en-to-end Quality of Service (QoS) guarantees in a distributed multimedia setting. Quality of Perception (QoP) is a term which encompasses not only a user's satisfaction with the quality of multimedia presentations, but also his/her ability to analyse, synthesise and assimilate the informational content of multimedia displays. The basics of a mapping linking QoP to QoS are then presented and the case for including it in an adaptable protocol is made. A proof of concept implementation based on the Dynamically Reconfigurable Protocol Stacks (DRoPS) project show that such applications can be used to improve QoP, especially in the case of dynamic and complex sequences

Mercury Concentrations in Fish Jerky Snack Food: Marlin, Ahi, and Salmon

<p>Abstract</p> <p>Background</p> <p>Dried meat and fish have served as an important durable nutrition source for humans for centuries. Because omega 3 fatty acids in fish are recognized as having antioxidant and anti inflammatory properties found to be beneficial for good health, many consumers are looking to fish as their main source of protein. Unfortunately, contaminants such as methylmercury can accumulate in some species of fish. The purpose of this research is to test commercially available fish jerky snack foods for mercury contamination.</p> <p>Methods</p> <p>Fifteen bags of marlin jerky, three bags of ahi jerky, and three bags of salmon jerky were purchased from large retail stores in Hawaii and California, and directly from the proprietors' Internet websites. Five individual strips of jerky per bag were analyzed for a total of one hundred and five tests.</p> <p>Results</p> <p>From the seventy-five marlin jerky samples, mercury concentration ranged from 0.052-28.17 μg/g, with an average of 5.53 μg/g, median 4.1 μg/g. Fifty-six (75%) marlin samples had mercury concentrations that exceeded the FDA's current mercury action level of 1.0 μg/g, while six samples had greater than 10 μg/g. Fifteen samples of ahi had mercury concentrations ranging from 0.09-0.55 μg/g, while mercury concentrations in fifteen salmon samples ranged from 0.030-0.17 μg/g.</p> <p>Conclusions</p> <p>This study found that mercury concentrations in some fish jerky can often exceed the FDA's allowable mercury limit and could be a significant source of mercury exposure.</p

Valuing Ecosystem Services in Semi-arid Rangelands through Stochastic Simulation

Ecosystem services and economic returns from semi-arid rangelands are threatened by land degradation. Policies to improve ecosystem service delivery often fail to consider uncertainty in economic returns gained through different land uses and management practices. We apply an analytical framework using stochastic simulation to estimate the range of potential monetary outcomes of rangeland ecosystem services under different land uses, including consideration of the uncertainty and variability of model parameters. We assess monetary and non-monetary dimensions, including those ecosystem services with uncertain and missing information, for communal rangelands, commercial ranches, game farms and Wildlife Management Areas in southern Kgalagadi District, Botswana. Public land uses (communal grazing areas and protected conservation land in Wildlife Management Areas) provide higher economic value than private land uses (commercial ranches and game farms), despite private land uses being more profitable in their returns from meat production. Communal rangelands and protected areas are important for a broader range of ecosystem services (cultural/spiritual services, recreation, firewood, construction material and wild food), which play a key role in sustaining the livelihoods of the largest share of society. The full range of ecosystem services should therefore be considered in economic assessments, while policies targeting sustainable land management should value and support their provision and utilisation. By forecasting the range of plausible ecosystem values of different rangeland land uses in monetary terms, our analysis provides policymakers with a tool to assess outcomes of land use and management decisions and policies

Alien Registration- Parent, Joseph B. (Van Buren, Aroostook County)

https://digitalmaine.com/alien_docs/32354/thumbnail.jp

A fresh look at the evolution and diversification of photochemical reaction centers

In this review, I reexamine the origin and diversification of photochemical reaction centers based on the known phylogenetic relations of the core subunits, and with the aid of sequence and structural alignments. I show, for example, that the protein folds at the C-terminus of the D1 and D2 subunits of Photosystem II, which are essential for the coordination of the water-oxidizing complex, were already in place in the most ancestral Type II reaction center subunit. I then evaluate the evolution of reaction centers in the context of the rise and expansion of the different groups of bacteria based on recent large-scale phylogenetic analyses. I find that the Heliobacteriaceae family of Firmicutes appears to be the earliest branching of the known groups of phototrophic bacteria; however, the origin of photochemical reaction centers and chlorophyll synthesis cannot be placed in this group. Moreover, it becomes evident that the Acidobacteria and the Proteobacteria shared a more recent common phototrophic ancestor, and this is also likely for the Chloroflexi and the Cyanobacteria. Finally, I argue that the discrepancies among the phylogenies of the reaction center proteins, chlorophyll synthesis enzymes, and the species tree of bacteria are best explained if both types of photochemical reaction centers evolved before the diversification of the known phyla of phototrophic bacteria. The primordial phototrophic ancestor must have had both Type I and Type II reaction centers

A systems approach to policy evaluation

There is growing interest in evaluating policy implementation in ways that grapple with the complexity of the process. This article offers an example of using systems methodology to explore how the child protection policy in child contact centres has functioned in practice. Rather than just asking the traditional evaluation question “is it working?” this study sought to understand how the policy was working and how it was interpreted as it interacted with other systems, producing conflicts, local variation and emergent effects. It illustrates how the systems concepts of ‘emergence’, ‘local rationality’, ‘socio-technical systems’ and ‘feedback for learning’ can contribute new knowledge and understanding to a complex policy evaluation problem

Mindlessness Revisited: Sequential Request Techniques Foster Compliance by Draining Self-control Resources

The present research extends previous findings suggesting that sequential request techniques, such as the Foot-in-the-Door (FITD) or Door-in-the-Face (DITF) technique, are primarily effective under conditions conducive of mindlessness. We forward that this mindlessness may be the product of the influence technique itself. More specifically, based on the notion of self-control as a limited resource, we hypothesize that actively responding to the initial request-phase of a FITD-compliance gaining procedure drains the target of his/her self-regulatory resources, thus creating the mindlessness so often observed in social influence settings. This resource depletion opens the door for compliance with the target request. The results were in line with these expectations. More specifically, we observed that active responding to an initial request of a FITD technique reduced the availability of self-regulatory resources. This state of resource depletion mediated the effect of the technique on behavioral compliance. In addition, the results of this study ruled out the alternate explanation that the effects were attributable to mood or a general tendency for acquiescence